A number of approaches have been proposed to target delivery of agents to cells and in particular to deliver agents across the blood brain barrier. Being able to deliver agents across the blood brain barrier is useful when treating CNS and neurodegenerative diseases.
The use of RNAi therapy such as siRNA for treating CNS diseases such as neurodegenerative diseases has been proposed. However problems with siRNA therapy for CNS diseases include: 1) siRNAs do not cross BBB, which is composed of tight junctions formed by endothelial cells surrounding the brain; and 2) they are not stable in the presence of serum nucleases.
Zimmerman et al (2006) reports complexing siRNA to liposomes to protect the siRNA from serum degradation and facilitate their uptake by the endocytic pathway. However liposomal methods may induce toxicity in neuronal cells.
Kumar et al (2007) and WO 2008/054544 disclose the use of a RVG peptide for targeting cells and delivering agents across the blood brain barrier. RVG-29 peptide specifically binds to the acetylcholine receptor (AchR) found on neuronal cells; however its relatively large size makes the peptide immunogenic and more susceptible to proteolytic degradation.
The invention aims to provide peptides that can be used for delivering agents to cells.